The goal of this proposal is to develop in vitro and in vivo models for the study of microbicide activity against Treponema pallidum (the causative agent of syphilis) and to utilize these systems to evaluate microbicidal preparations under consideration for sexually transmitted disease prevention. Our laboratory has used a tissue culture system that supports limited multiplication of T. pallidum to study the spirochete's physiology, growth requirements, and antimicrobial susceptibility. In Specific Aim 1, this in vitro culture system will be used to screen microbicidal compounds for activity against T. pallidum and to determine their minimal inhibitory and bactericidal concentrations. Candidate compounds to be tested in this system include C31G, nonoxynol-9, gramicidin, and other agents likely to have treponemicidal activity. Information from these studies will be used to determine the effective concentration ranges of microbicides for use in in vivo activity of microbicides. An abraded skin model will permit the direct evaluation of the ability of microbicides to block transepidermal infection. A rabbit vaginal model will also be investigated as a means of evaluating the activity of microbicides in preventing infection by this route. In Specific Aim 3, the human vaginal xenograft -SCID mouse model under development in Dr. kreider's laboratory will be examined for its ability to support the growth and pathogenesis of T. pallidum. If successful, this model could be used to confirm the ability of treponemicidal agents to present the infection of human vaginal tissue. The information resulting from this project will be combined with the results of the other projects in this proposal to design the best combination of microbicidal agents for the prevention of viral and bacterial sexually transmitted infections.